Journal Article

Male–female phenotype correlation and dissociation related to mutations in the ARX gene

Li, Chumei Li

2024

Overview

The mother, all her three affected sons as well as a niece and daughter of this woman’s sister (who was not tested), were all found to carry a mutation in their ARX gene RefSeq NM_139058.3: c.441_464dup p.Ala148_Ala155dup, resulting in a polyalanine repeat tract in the ARX protein. Figure 2 of Gras et al1 and figure 2 of Mattiske et al2 together appear to have shown that mutations in the ARX gene within and flanking the homeodomain as well as near the junction between exons 4-5 appear far more likely to be associated with severe/moderate phenotype in both females and males; both nonsense and missense mutations near the 5’ NH2 region, roughly before amino acid p.40 in exon one, appeared to be associated with normal phenotype in carrier females, but severe male phenotype; mutations near the 3’ COOH of the coding region, near and within the Aristaless domain also seem to be well tolerated by females but are typically associated with a severe/moderate phenotype in males; genotype-phenotype correlation appears to be more variable for mutations outside the above-mentioned regions. (II) From figure 2 of Gras et al (2024) showing positions of mutations from 5’ NH2 to 3’ COOH of the ARX gene and corresponding phenotypic severity in male and female patients.

• Publisher: BMJ Publishing Group Ltd,BMJ Publishing Group LTD
• Subject: Amino acids / ARX protein / Asymptomatic / Exons / Females / Genetics, Medical / Genotype / Genotype & phenotype / Genotypes / Homeobox / Intellectual disabilities / Males / Missense mutation / Mutation / Phenotype / Phenotypes / Polyalanine